The aim of this animal study in sheep was to investigate the safety and efficacy of a novel multi-phosphonate surface treatment, SurfLink®
, on commercially rough and machined titanium dental implants after 2, 8, and 52 weeks. While the healing period of two to eight weeks should correspond to the phase of early implant integration, results after 52 weeks should provide information for the mid- to long-term outcome [35
This novel surface treatment was shown to covalently bind to the oxide layer of the titanium implant surface [34
]. In virtue of its chemical structure the treatment is stable against chemical and enzymatic hydrolysis, and is, thus, permanently attached to the implant surface under physiological conditions. Whereas conventional micro-structured and moderately rough dental implants rely on mechanical interlocking [37
], this surface treatment was designed to provide a linker which results in a rapidly established and stable chemical bone-to-implant interface. In a preliminary study in a rat model, significant increases in early fixation were observed [38
]. The first clinical results with multi-phosphonate treated dental implants showed at one-year post-loading an excellent outcome with no implant failures and maintaining marginal bone levels, while control implants lost a significant amount of marginal bone after loading [39
The experimental setup for this study was a pelvic sheep model, as used in previous studies investigating the osseointegration properties of various implant designs and surfaces [40
]. Sheep animal models are well-established in orthopaedic research for analyzing fracture healing, new osteosynthesis techniques and also osseointegration of implants, because they exhibit a very similar lamellar bone structure to humans [41
]. Furthermore, bone from the sheep pelvic region resembles a bone structure similar to the human mandible mimicking a more cancellous structure in the cranial part with increasing cortical thickness towards the caudal part. Additionally, overlying muscle tissues also reflect some slight intermittent biomechanical forces on the supracrestal implant parts. This sheep model was found to be economical in its use of animals, it provided the intra- and inter individual data for statistical comparison and it was associated with a zero failure rate of surgery [44
]. In contrast to an alternative and also well-established animal model using beagle dogs, the sheep model used in this study avoided an ongoing and stimulating bony process by previous manipulation through dental extractions. In addition it excludes the 2.5-fold higher bone remodeling rate and post-operative complications like poor mouth hygiene commonly associated with other animal models [45
]. However, the soft tissue interface and microbiological issues could not be scrutinized in this model. Together with the fact that the pelvic shaft model presents a prosthodontically unloaded experimental set-up in periphery bone, this can be seen as critical drawback for evaluating long-term success in a dental clinical environment [46
]. Nevertheless, since animal models are always an approximation, it is wise to take a stepwise approach and first test biocompatibility and osseointegration under non-complicated conditions before adding the next complex question of soft tissue and bacterial interference.
Due to its phosphonic functional groups, the multi-phosphonate surface treatment has been found to increase hydrophilicity and wettability of implant surfaces and thus an increase in affinity of blood, proteins and bone cells for the implant surface is expected. Once on the implant surface, bone cells quickly spread along the multi-phosphonate treated implant as shown by Figure 4
(2 weeks). The increased bone in contact with the multi-phosphonate treated implant results in greater biomechanical implant fixation.
Biomechanical stability of implants with the multi-phosphonate treatment tended to result in superior torque values after 2 weeks, especially when combined with a rough implant surface, which resulted in significantly (p
= 0.036, RW, pairwise comparison) higher removal torque values (Figure 1
). Additionally, the multi-phosphonate treated Wet machined implants (MW) showed tendencies for greater torque and stiffness values at all time points when compared to control machined implants (MC) (Figure 1
and Figure 2
). These results corroborate previously published data from a study in rats [38
], whereby a significant increase in pull-out strength (+38%, p <
0.01) for the multi-phosphonate treated cylinders was observed.
Biomechanical data was confirmed by the histology results, which showed positive tendencies for the multi-phosphonate treated implants.
While cortical bone generally provides sufficient primary stability, increased implant failure rates are often observed in areas with loose trabecular bone like in the posterior maxilla [47
]. Hence, evaluation of the BIC was also conducted considering cortical and cancellous bone structures separately. After 8 weeks ongoing active peri-implant bone remodeling processes led to an overall decline of Total BIC (Table 2
) in all groups indicating the interval of reduced implant stability between the second and third healing phase during the osseointegration process. Nevertheless, the results showed that at 8 and 52 weeks all the multi-phosphonate treated surfaces had tendencies for increased Total BIC (from pair-wise analysis, data not shown).
Histomorphometrical evaluation exhibited significant production of new bone at the interface of all implant surfaces between two and eight weeks (Figure 6
), also indicative of normal active bone remodeling taking place after implantation. An increased new-old bone ratio was observed on the multi-phosphonate treated rough Dry implants (RD: +44%, pair-wise analysis) at 2 weeks and on the multi-phosphonate treated machined Dry surfaces at eight weeks (MD: +35%, p =
0.039, pair-wise analysis, Figure 8
). Indeed the higher magnification histological images showed that the multi-phosphonate treated surfaces are osteoconductive, with bone cells quickly spreading out from contact points to cover the implant surface, resulting in greater woven bone matrix formation on the implant. A close-up of the multi-phosphonate treated implant shows mineralised bone, osteoid and lining osteoblasts directly at the surface (Figure 5
) as early as two weeks (Figure 4
). This behavior was not observed on control implants at either two or eight weeks (Figure 4
The positive tendencies seen in the biomechanical and BIC analyses of the multi-phosphonated treated surfaces were supported by the SEM images of the bone to implant interface (Figure 9
). On the multi-phosphonated treated implants bone remodeling and mineral deposition were observed at several places, both in cortical and cancellous bone. Furthermore, at 52 weeks, rupture after torque testing occurred within the mature lamellar bone rather than at the bone to implant interface, suggesting a strong bond of the surrounding bone to the multi-phosphonated treated implant, as also seen in Figure 5
. On control implant surfaces the same kind of organic features were observed, but less abundantly than on the multi-phosphonated treated implants. Inspection of the lamellar bone remnants showed fracture at the bone to implant interface more frequently than within bone.
To the authors knowledge there are no commercially available similar technologies to the multi-phosphonate surface treatment. Hydroxyapatite (HA) coating is seen as the gold standard of biomimetic implant surface coatings. However, while preclinical testing has been mostly positive, some studies have reported less favorable results [8
]. To date, clinical trials have failed to show a difference in clinical outcome for HA treated dental implants. Furthermore, long term HA-coated implant stability is uncertain [49
] and it remains clinically unproven [50
The first clinical results of multi-phosphonate treated implants were recently reported in the literature [39
]. One year post-loading results from a Randomized Controlled clinical Trial (RCT) showed that the multi-phosphonate treated implants were well osseointegrated. Furthermore, the data suggested a tendency for reduced peri-implant bone loss. The difference between multi-phosphonate treated and control implants was quasi-significant (p =
0.057). It must be noted that the number of patients included in the analysis was only 21. Long-term follow-ups will be reported at three years and five years post-loading.
Statistical analysis of the biomechanical and BIC data in this animal study showed significant differences (p <
0.05 and p <
0.01, respectively, from ANOVA statistical analysis) between rough and machined implants, irrespective of the treatment after 2, 8, and 52 weeks. This is in accordance with the well-known concept that surface micro-roughness of implants in the range of 1–10 µm affects the rate of osseointegration and mechanical fixation by maximal interlocking of bone matrix and implant surface [14
It has been noted that there is a lack of statistically significant differences in BIC between treated and control groups for either surfaces. It must be considered that this is an optimized experimental design in an unloaded and uncomplicated situation and the commercial titanium implant system used for all groups enjoys a high rate of clinical success [52
]. From our experience with the same animal model a drop in BIC and torque values of up to 50% can be seen depending on implant design and material of dental implants [7
]. In clinical reality, implant failures are dependent on many factors, and not just the implant itself. Soft tissue integrity, bacterial contamination and the surgeon’s manual capabilities are among these factors that may finally determine if dental implants belong to the category of 2%–5% failures or success [53
]. Indeed, the clinical results obtained with the multi-phosphonate treated implants [39
] suggest that this novel treatment may affect the early integration and immediate sealing of an implant, particularly in a compromised bone situation (e.g., soft tissue-bone, bone augmentation), thus, minimizing the overall and individual implant failure rates.